Linear No-threshold (LNT) vs. Hormesis: Paradigms, Assumptions, and Mathematical Conventions that Bias the Conclusions in Favor of LNT and Against hormesis.

The linear no-threshold assumption misunderstands the complex multiphasic biological response to ionizing radiation, focusing solely on the initial physical radiogenic damage. This misunderstanding is enabled (masked and amplified) by a number of mathematical approaches that bias results in favor of linear no-threshold and away from alternatives, like hormesis, that take biological response into account. Here we explore a number of these mathematical approaches in some detail, including the use of frequentist rather than Bayesian statistical rules and methods.

A strategy for early-risk predictions of clinical drug-drug interactions involving the GastroPlus DDI module for time-dependent CYP inhibitors.

1. A set of reference compounds for time-dependent inhibition (TDI) of cytochrome P450 with available literature data for k and K was used to predict clinical implications using the GastroPlus software. Comparisons were made to in vivo literature interaction data.

Epidemiology Without Biology: False Paradigms, Unfounded Assumptions, and Specious Statistics in Radiation Science (with Commentaries by Inge Schmitz-Feuerhake and Christopher Busby and a Reply by the Authors).

Radiation science is dominated by a paradigm based on an assumption without empirical foundation. Known as the linear no-threshold (LNT) hypothesis, it holds that all ionizing radiation is harmful no matter how low the dose or dose rate. Epidemiological studies that claim to confirm LNT either neglect experimental and/or observational discoveries at the cellular, tissue, and organismal levels, or mention them only to distort or dismiss them.

Protein kinase C-alpha and -epsilon are enriched in growth cones of differentiating SH-SY5Y human neuroblastoma cells.

SH-SY5Y cells differentiate into neuronal-like cells and express marker proteins like growth-associated protein (GAP-43) and neuropeptide tyrosine when treated with a low concentration (16 nM) of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of growth factors or serum. Both control and differentiated cells expressed protein kinase C-alpha (PKC-alpha), PKC-epsilon, and PKC-zeta as revealed by Western blot analyses, but the subcellular distribution of the three isoforms was not uniform, indicating specific localized functions of the enzymes. In growth cones prepared from differentiating cells PKC-alpha and PKC-epsilon were enriched.